Abstract
Background
Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most common causes of idiopathic nephrotic syndrome (INS). We have evaluated the reliability of urinary neutrophil-gelatinase-associated lipocalin (uNGAL), urinary alpha1-microglobulin (uα1M) and urinary N-acetyl-beta-D-glucosaminidase (uβNAG) as markers for differentiating MCD from FSGS. We have also evaluated whether these proteins are associated to INS relapses or to glomerular filtration rate (GFR).
Methods
The patient cohort comprised 35 children with MCD and nine with FSGS; 19 healthy age-matched children were included in the study as controls. Of the 35 patients, 28 were in remission (21 MCD, 7 FSGS) and 16 were in relapse (14 MCD, 2 FSGS). The prognostic accuracies of these proteins were assessed by receiver operating characteristic (ROC) curve analyses.
Results
The level of uNGAL, indexed or not to urinary creatinine (uCreat), was significantly different between children with INS and healthy children (p = 0.02), between healthy children and those with FSGS (p = 0.007) and between children with MCD and those with FSGS (p = 0.01). It was not significantly correlated to proteinuria or GFR levels. The ROC curve analysis showed that a cut-off value of 17 ng/mg for the uNGAL/uCreat ratio could be used to distinguish MCD from FSGS with a sensitivity of 0.77 and specificity of 0.78. uβNAG was not significantly different in patients with MCD and those with FSGS (p = 0.86). Only uα1M, indexed or not to uCreat, was significantly (p < 0.001) higher for patients in relapse compared to those in remission.
Conclusions
Our results indicate that in our patient cohort uNGAL was a reliable biomarker for differentiating MCD from FSGS independently of proteinuria or GFR levels.
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References
Bennett MR, Piyaphanee N, Czech K, Mitsnefes M, Devarajan P (2012) NGAL distinguishes steroid sensitivity in idiopathic nephrotic syndrome. Pediatr Nephrol 27:807–12
Lahdenkari AT, Suvanto M, Kajantie E, Koskimies O, Kestilä M, Jalanko H (2005) Clinical features and outcome of childhood minimal change nephrotic syndrome: is genetics involved? Pediatr Nephrol 20:1073–80
Eddy AA, Symons JM (2003) Nephrotic syndrome in childhood. Lancet 362:629–39
Cattran DC, Rao P (1998) Long-term outcome in children and adults with classic focal segmental glomerulosclerosis. Am J Kidney Dis 32:72–9
Roberti I, Vyas S (2010) Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol 25:1117–24
Sesso R, Santos AP, Nishida SK, Klag MJ, Carvalhaes JT, Ajzen H, Ramos OL, Pereira AB (1992) Prediction of steroid responsiveness in the idiopathic nephrotic syndrome using urinary retinol-binding protein and beta-2-microglobulin. Ann Intern Med 116:905–9
Portman RJ, Kissane JM, Robson AM (1986) Use of beta 2 microglobulin to diagnose tubulo-interstitial renal lesions in children. Kidney Int 30:91–8
Calişkan S, Hacibekiroğlu M, Sever L, Ozbay G, Arisoy N (1996) Urinary N-acetyl-beta-D-glucosaminidase and beta 2-microglobulin excretion in primary nephrotic children. Nephron 74:401–4
Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637
Gao A, Cachat F, Faouzi M, Bardy D, Mosig D, Meyrat BJ, Girardin E, Chehade H (2012) Comparison of the glomerular filtration rate in children by the new revised Schwartz formula and a new generalized formula. Kidney Int 83:524–530
DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44:837–845
Youden WJ (1950) Index of rating diagnostic tests. Cancer 3:32–35
Vallés P, Peralta M, Carrizo L, Martin L, Principi I, Gonzalez A, Manucha W (2000) Follow-up of steroid-resistant nephrotic syndrome: tubular proteinuria and enzymuria. Pediatr Nephrol 15:252–8
Woroniecki RP, Orlova TN, Mendelev N, Shatat IF, Hailpern SM, Kaskel FJ, Goligorsky MS, O’Riordan E (2006) Urinary proteome of steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome of childhood. Am J Nephrol 26:258–67
Woroniecki RP, Shatat IF, Supe K, Du Z, Kaskel FJ (2008) Urinary cytokines and steroid responsiveness in idiopathic nephrotic syndrome of childhood. Am J Nephrol 28:83–90
Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, Buemi M (2008) Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis 52:595–605
Nejat M, Hill JV, Pickering JW, Edelstein CL, Devarajan P, Endre ZH (2012) Albuminuria increases cystatin C excretion: Implications for urinary biomarkers. Nephrol Dial Transplant 0:1–8
Thielemans N, Lauwerys R, Bernard A (1994) Competition between albumin and low-molecular-weight proteins for renal tubular uptake in experimental nephropathies. Nephron 66:453–458
Bernard A, Viau C, Ouled A, Lauwerys R (1987) Competition between low- and high-molecular-weight proteins for renal tubular uptake. Nephron 45:115–118
Bernard A, Amor AO, Viau C, Lauwerys R (1988) The renal uptake of proteins: a non selective process in conscious rats. Kidney Int 34:175–185
Kaseda R, Iino N, Hosojima M, Takeda T, Hosaka K, Kobayashi A, Yamamoto K, Suzuki A, Kasai A, Suzuki Y, Gejyo F, Saito A (2007) Megalin-mediated endocytosis of cystatin C in proximal tubule cells. Biochem Biophys Res Commun 357:1130–1134
Stickler GB, Hayles AB, Power MH, Ulrich JA (1960) Renal tubular dysfunction complicating the nephrotic syndrome. Pediatrics 26:75–85
Cameron JS (1990) Proteinuria and progression in human glomerular diseases. Am J Nephrol 10:81–7
Wasilewska A, Zoch-Zwierz W, Taranta-Janusz K, Michaluk-Skutnik J (2010) Neutrophil gelatinase-associated lipocalin (NGAL): a new marker of cyclosporine nephrotoxicity? Pediatr Nephrol 25:889–97
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Chehade, H., Parvex, P., Poncet, A. et al. Urinary low-molecular-weight protein excretion in pediatric idiopathic nephrotic syndrome. Pediatr Nephrol 28, 2299–2306 (2013). https://doi.org/10.1007/s00467-013-2569-6
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DOI: https://doi.org/10.1007/s00467-013-2569-6